The vestibuloocular reflex (VOR) normally moves the eyes opposite that of head rotation in order to stabilize the visual image on the retina. VOR gain (response-stimulus) has been known to adapt to a new value alter a long-term modification of the sensory input and thus stabilize the retinal image to facilitate visual processing performed elsewhere in the brain. This proposal will study the origins of this neural plasticity in the cerebellum and brainstem during visual and vestibular mismatch produced in vitro. Using a novel in vitro turtle brain preparation with the eyes and temporal bone attached, natural sensory stimuli will provide inputs for long-term VOR adaptation. Visual patterns of whole field visual motion will be imaged onto the entire retinal surface, while the entire preparation is rotated on a rate table. Preliminary results show that under these conditions, normal visual and vestibular responses are elicited by the first order neurons in the brainstem. The velocity of visual pattern motion is encoded in neurons of the accessory optic system (Basal Optic Nucleus) and pretectum (Mesencephalic Lentiform Nucleus), while volcity of the head rotation of head rotation is encoded in the vestibular nucleus. Responses to either of these sensory signals have also been recorded in the cerebellar cortex. This turtle brain preparation remains responsive to these natural sensory stimuli after days in vitro. There are three aims of this project. First, neurons will be identified in pathways involved in adaptive changes of the VOR; the cerebellar cortex and vestibular nucleus. Second, the normal visual and vestibular responses of these neurons will be characterized using sinusoidal stimuli. Finally, the brain will be exposed to both sensory stimuli simultaneously and continuously, such that visual motion will signal an instability in the retinal image along the same axis as the rotation of the head that drives the oculomotor reflex. Within hours of exposure to these paired sensory signals, it is expected that the response to vestibular stimulation alone will change, in an attempt to reduce the instability in the retinal image. This study will identify the adaptive cells, their response properties, and the time course of adaptation. This project also develops an experimental preparation in which future intracellular studies can determine the synaptic mechanisms by which neural plasticity is generated and can identify its presynaptic and post-synaptic components. A full understanding of this neural process may lead to better treatments for visual and balance disorders.